Biohybrids (a combination of biological material and inorganic nanoparticles) offer a number of advantages like improved functionality over conventional materials.Thus, to understand the practical application of biohybrids as drug carriers, a biohybrid drug carrier of colloidal silica nanoparticles (NP)-sodium alginate loaded with doxorubicin (Dox-biohybrid) was synthesized by evaporation induced self-assembly (EISA) using spray drying technique. Further, the morphology, size and interactions between various components of the biohybrid were studied through SEM, DLS and FTIR techniques. The drug loading efficiency, release profile, cellular uptake and cytotoxicity of Dox-biohybrid was investigated and compared with free Dox. The drug loading efficiencies of Dox-biohybrid, Dox-silica NP and Dox-sodium alginate were 93.7 %, 96.4 % and 88.3 % respectively. In vitro release study showed a slow release of entrapped Dox from Dox-biohybrid as compared to other carriers. This release was also pH-responsive with significantly higher cumulative drug release at pH 5.5 (cancer microenvironment) in comparison to pH 7.4 (physiological conditions). The empty biohybrid carrier did not show cytotoxicity to normal mouse lymphocytes upto a concentration of 25 μg/mL which was used further. https://www.selleckchem.com/products/propionyl-l-carnitine-hydrochloride.html The uptake of Dox from Dox-biohybrid by A549 cells was more than 2fold as compared to uptake from free Dox. in vitro viability assay revealed that treatment of lung carcinoma A549 cells with Dox-biohybrid resulted in 50 % loss of cell viability at 500 nM, compared to only 12 % loss with free Dox. Thus, we report the synthesis of a novel biohybrid drug delivery system by means of spray drying process that has promising applications in cancer treatment.Chemodynamic therapy (CDT), inducing tumor cell apoptosis through Fenton reaction to produce hydroxyl radical (?OH), is an emerging cancer treatment technology. Highly efficient Fenton catalytic reactions usually take place at a low pH environment. Utilizing graphitic carbon nitride supported hemin and Au nanoparticles (g-C3N4/hemin/Au) as a novel biomimetic nanocatalyst, we achieve an enhanced CDT for inducing tumor cell apoptosis in the presence of excess H2O2, and reveal the molecular events during the CDT-induced apoptosis. The prepared g-C3N4/hemin/Au nanohybrids exhibit excellent Fenton catalytic activity for the generation of highly toxic ?OH at weak acidic and neutral condition, which breaks through the limitation of traditional acidity-dependent response. The Fenton catalytic mechanism was also studied. The Fenton efficiency is primarily enhanced by the high affinity between nanohybrids and H2O2, and the transformation of Fe(III) to Fe(IV)=O without the formation of iron hydrate precipitation. Moreover, the intracellular molecular events during the CDT process were monitored. Phenylalanine metabolism was perturbed with protein degradation and DNA structures were damaged, which eventually lead to cell apoptosis. This study provides a significant guidance for the further development of more effective CDT platforms.Metabolic syndrome (MetS) is associated with dementia, but it is unclear whether MetS is related to Alzheimer's disease (AD). We investigated the association of MetS with brain amyloid, a key AD feature, and neurodegeneration. A community-based sample of 350 middle-aged Hispanics in New York City had cerebral amyloid β (Aβ) burden ascertained with 18F-Florbetaben positron emission tomography. Neurodegeneration was ascertained as cortical thickness in AD signature regions from 3T brain MRI. MetS and its components (glucose, blood pressure, triglycerides, high-density lipoprotein, adiposity) were defined using the National Institutes of Health criteria. Neither the presence of MetS nor the MetS score was associated with Aβ or neurodegeneration. Among the MetS components, elevated glucose was associated with lower Aβ burden, and this association was not explained by diabetes treatment. Glucose and triglycerides were related to smaller cortical thickness. Our findings suggest that MetS as an arbitrary measure of aggregate metabolic and vascular risk does not capture the risk of AD neuropathology in late middle age and that other approaches to measure the aggregate risk should be examined.Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus. High glucose has resulted in oxidative stress and following renal fibrosis as the crucial nodes of this disease. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating transcription of many antioxidant genes and suppressing synthesis of extracellular matrix. To discover Nrf2 activators targeting DN, we have evaluated polypodiside using cell-based assays. The results showed polypodiside inhibited the high glucose-induced self-limited proliferation of glomerular meangial cells. Activation of Nrf2 and enhanced transcription to antioxidant response elements were observed in the presence of polypodiside. Oxidative stress and accumulation of extracellular matrix induced by high glucose in glomerular meangial cells have been ameliorated by polypodiside. Further investigations revealed the effects of polypodiside on glomerular meangial cells were associated with activation of Nrf2. Co-immunoprecipitation of Nrf2 disclosed polypodiside disrupted the Kelch-like ECH-associated protein-1 (Keap1)-Nrf2 interaction. Molecular docking elucidated polypodiside could enter the Nrf2 binding cavity of Keap1 via interacting with the residues encompassing that cavity. These findings indicate polypodiside is a Keap1-dependent Nrf2 activator affording the catabatic effects against oxidative stress and accumulation of extracellular matrix in glomerular meangial cells under high glucose.Malaria is a disease that requires new drugs not only to fight Plasmodium but also to reduce symptoms of infection such as fever and inflammation. A series of 21 hybrid compounds were designed from chloroquine (CQ) and primaquine (PQ) linked to the pharmacophoric group present in phenylacetic anti-inflammatory drugs. These compounds were designed to have dual activity namely, to be capable of killing Plasmodium and still act on the inflammatory process caused by malaria infection. The compounds were assayed with nine different biological methods. The carbonylated CQ derivative 6 (n = 3; R1 = Cl) was more potent than CQ in vitro, and 8 (n = 4; R1 = H) reduced P. berghei parasitemia up to 37% on day 7. The carbonylated PQ derivative 17 (R = Br) was slightly less potent than PQ. The gem-difluoro PQ derivative 20 (R = Cl) exhibited high transmission blockade of the malaria sporogonic cycle in mosquitoes. Compounds 6 and 20 dose-dependently reduced nitric oxide (NO) production and inhibited TNFα production by LPS-stimulated J774A.